Biological psychiatry
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Biological psychiatry · Apr 2012
β-arrestin2 regulates cannabinoid CB1 receptor signaling and adaptation in a central nervous system region-dependent manner.
Cannabinoid CB(1) receptors (CB(1)Rs) mediate the effects of ▵(9)-tetrahydrocannabinol (THC), the psychoactive component in marijuana. Repeated THC administration produces tolerance and dependence, which limit therapeutic development. Moreover, THC produces motor and psychoactive side effects. β-arrestin2 mediates receptor desensitization, internalization, and signaling, but its role in these CB(1)R effects and receptor regulation is unclear. ⋯ β-arrestin2 regulation of CB(1)R signaling following acute and repeated THC administration was region-specific, and results suggest that multiple, overlapping mechanisms regulate CB(1)Rs. The observations that βarr2-KO mice display enhanced antinociceptive responses to acute THC and decreased tolerance to the antinociceptive effects of the drug, yet enhanced tolerance to catalepsy, suggest that development of cannabinoid drugs that minimize CB(1)R interactions with β-arrestin2 might produce improved cannabinoid analgesics with reduced motor suppression.
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Biological psychiatry · Apr 2012
Evidence of a dissociation pattern in resting-state default mode network connectivity in first-episode, treatment-naive major depression patients.
Imaging studies have shown that major depressive disorder (MDD) is associated with altered activity patterns of the default mode network (DMN). However, the neural correlates of the resting-state DMN and MDD-related pathopsychological characteristics, such as depressive rumination and overgeneral autobiographical memory (OGM) phenomena, still remain unclear. ⋯ We report dissociation between anterior and posterior functional connectivity in resting-state DMNs of first-episode, treatment-naive young adults with MDD. Increased functional connectivity in anterior medial regions of the resting-state DMN was associated with rumination, whereas decreased functional connectivity in posterior medial regions was associated with OGM. These results provide new evidence for the importance of the DMN in the pathophysiology of MDD and suggest that abnormal DMN activity may be an MDD trait.